The overall objective of this investigation is to provide a better understanding of the hemodynamics of the flow of sickle cells in the microcirculation especially as related to microvascular occlusion. To achieve this objective high resolution "in vivo" microscopic and electro-optical methods will be used to quantitate the behavior of these cells in and with the microvasculature of small laboratory animals. When compared with the behavior of normal human erythrocytes and the animals own cells, the results of this study should: (a) provide data on the "in vivo" behavior of sickle cells in the microcirculation; (b) test the validity of using the transfused animal as a model for studying the behavior of human sickle cells in the microcirculation; and (c) determine what differences exist in the behavior of sickle cells in vivo between patients having differing severities of the disease, and how these differences relate to differences in whole blood viscosity measured "in vitro". Once a better understanding of the hemodynamics of sickle cells in the microcirculation has been obtained and the validity of the transfused animal model assessed, the efficacy of various drugs in reversing or preventing sickling "in vivo" will be evaluated using the animal model. In summary, it is anticipated that the results of this investigation should help to elucidate the patho-physiology of the vaso-occlusive crisis and provide some additional direction for its treatment.